ALS (Amyotrophic Lateral Sclerosis)Phase 2NCT07294144
Tofersen in Non-SOD1 ALS
A Phase 2 study testing Tofersen in people with ALS (Amyotrophic Lateral Sclerosis), run by Washington University School of Medicine at 3 sites in United States.
Trial summary
The goal of this clinical trial is to evaluate whether tofersen is safe and effective in adults with non-SOD1 ALS. Tofersen is currently approved by the U.S. Food and Drug Administration to treat SOD1-ALS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALS (Amyotrophic Lateral Sclerosis)
- What is being tested?
- Tofersen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Dec 2025to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local participant privacy regulations.
- Aged 18 years or older at the time of informed consent.
- Confirmed diagnosis of ALS.
- Time since onset of weakness due to ALS ≤ 24 months at the time of the screening visit.
- Prior confirmed genetic testing negative for SOD1 and FUS mutations. Participants with mutations in genes other than SOD1 and FUS may be enrolled at the discretion of the Site Investigator.
- SVC ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
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- Medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
- All participants must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
- If taking riluzole, participant must be on a stable dose for ≥ 30 days prior to Day 1 and expected to remain at that dose until the final study visit.
- If taking edaravone, participant must have initiated edaravone ≥ 60 days (2 treatment cycles) prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study.
Who cannot join
- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use or expanded access programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
- Current enrollment in any other interventional study.
- History of drug abuse or alcoholism within ≤ 6 months of study enrollment that would limit participation in the study, as determined by the Investigator.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
- Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that according to the Investigator would interfere with the conduct or assessments of the study.
- History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in neurofilament, in the opinion of the Investigator.
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- Female participants who are pregnant or currently breastfeeding.
- Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days, as determined by the Investigator.
- History of allergies to a broad range of anesthetics.
- Tracheostomy.
- Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
- Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication that cannot be safely held before and/or after an LP procedure according to local or institutional guidelines and/or Investigator determination.
- Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
- Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment.
- Inability to comply with study requirements.
- Other unspecified reasons that, in the opinion of the Investigator, make the participant unsuitable for enrollment.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Karon Simmons, 404-712-4182, kmsimm2@emory.edu
Jonathan Glass, MD
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Miranda Durcan, 617-643-9550, tofersensporadichealey@mgb.org
Suma Babu, MBBS, MPH
- Recruiting
Washington University ALS Center
St Louis, Missouri, 63110
ALS Clinical Research Team, 1-844-257-2273, als@wustl.edu
Timothy M Miller, MD, PhD
About this study
Official title: A Study to Evaluate the Biological Effect of Tofersen in Adults With Amyotrophic Lateral Sclerosis Without Mutations in SOD1
The goal of this clinical trial is to evaluate whether tofersen is safe and effective in adults with non-SOD1 ALS. Tofersen is currently approved by the U.S. Food and Drug Administration to treat SOD1-ALS. The main questions it aims to answer are:
- Does tofersen lower the levels of neurofilament light chain (NfL) in the blood and CSF of adult participants with non-SOD1 ALS?
- Is tofersen safe and tolerable for adult participants with non-SOD1 ALS?
- Does tofersen affect other measurements such as clinical outcomes and quality-of-life measures in participants with non-SOD1 ALS?
Read more
Participants will :
- Receive 100mg tofersen via lumbar puncture for 24 weeks. The doses are at the following time points: Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
- Complete 2 follow-up visits following the end of the dosing period at Weeks 28 and 32.
- Complete a variety of questionnaires and outcome measurements such as strength and breathing testing.
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Being tested
- Tofersen
- Keywords
- als, amyotrophic lateral sclerosis, tofersen, qalsody
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofersenDrug
Tofersen 100 mg administered intrathecally.
| Study group | Role | What they receive |
|---|---|---|
| Tofersen | Experimental | Not described Receives: Drug: Tofersen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with ≥30% reduction in plasma NfL
Measured: From Baseline to Week 28
Secondary outcomes (3)
Proportion of participants with ≥ 30% reduction in CSF NfL
Measured: From Baseline to Week 28
Change in plasma and CSF NfL levels
Measured: From Baseline to Week 28
Incidence of adverse events and serious adverse events
Measured: From Baseline through study completion, an average of 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2025
- Study start29 Dec 2025
- Primary completionJan 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALS (Amyotrophic Lateral Sclerosis)Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Principal investigator, Timothy M. Miller, MD, PhD, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07294144
- Sponsor's protocol ID
- US-TOF-12361
- Status last verified
- Jun 2026
- First submitted
- 15 Dec 2025
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Biological Effect of Tofersen in Adults With Amyotrophic Lateral Sclerosis Without Mutations in SOD1
- ClinicalTrials.gov ID
- NCT07294144
- Acronym / sponsor ID
- US-TOF-12361
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Keywords
- als, amyotrophic lateral sclerosis, tofersen, qalsody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- 29 Dec 2025 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 19 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate whether tofersen is safe and effective in adults with non-SOD1 ALS. Tofersen is currently approved by the U.S. Food and Drug Administration to treat SOD1-ALS. The main questions it aims to answer are:
- Does tofersen lower the levels of neurofilament light chain (NfL) in the blood and CSF of adult participants with non-SOD1 ALS?
- Is tofersen safe and tolerable for adult participants with non-SOD1 ALS?
- Does tofersen affect other measurements such as clinical outcomes and quality-of-life measures in participants with non-SOD1 ALS?
Participants will :
- Receive 100mg tofersen via lumbar puncture for 24 weeks. The doses are at the following time points: Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
- Complete 2 follow-up visits following the end of the dosing period at Weeks 28 and 32.
- Complete a variety of questionnaires and outcome measurements such as strength and breathing testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tofersen | Experimental | Drug: Tofersen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local participant privacy regulations.
- Aged 18 years or older at the time of informed consent.
- Confirmed diagnosis of ALS.
- Time since onset of weakness due to ALS ≤ 24 months at the time of the screening visit.
- Prior confirmed genetic testing negative for SOD1 and FUS mutations. Participants with mutations in genes other than SOD1 and FUS may be enrolled at the discretion of the Site Investigator.
Key exclusion criteria (16 listed)
- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use or expanded access programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
- Current enrollment in any other interventional study.
- History of drug abuse or alcoholism within ≤ 6 months of study enrollment that would limit participation in the study, as determined by the Investigator.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
- Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that according to the Investigator would interfere with the conduct or assessments of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TofersenTofersen 100 mg administered intrathecally. | Drug | Tofersen |
Primary outcome
Proportion of participants with ≥30% reduction in plasma NfL
Time frame: From Baseline to Week 28
3 secondary outcomes
Proportion of participants with ≥ 30% reduction in CSF NfL
Time frame: From Baseline to Week 28
Change in plasma and CSF NfL levels
Time frame: From Baseline to Week 28
Incidence of adverse events and serious adverse events
Time frame: From Baseline through study completion, an average of 8 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tofersen in people with ALS (Amyotrophic Lateral Sclerosis), run by Washington University School of Medicine at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with ≥30% reduction in plasma NfL (time frame: From Baseline to Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.